Alternative polyadenylation directs tissue-specific miRNA targeting in Caenorhabditis elegans somatic tissues, pp. 757-774
Stephen M. Blazie, Heather C. Geissel, Henry Wilky, Rajan Joshi, Jason Newbern, and Marco Mangone
Alternative polyadenylation (APA) is observed in virtually all metazoans and results in mRNA isoforms with different 3’ends. It is routinely detected and can be altered in disease, but its biological role is still a mystery. Blazie et al. performed an in-depth analysis of the transcriptome and APAome of eight somatic tissues in worms and show mechanistic evidence that tissue-specific APA is used to evade miRNA regulation. This work also provides the first comprehensive tissue-specific worm transcriptome and APAome resource.
Increased power to dissect adaptive traits in global sorghum diversity using a Nested Association Mapping population, pp. 573-585
Sophie Bouchet, Marcus O. Olatoye, Sandeep R. Marla, Ramasamy Perumal, Tesfaye Tesso, Jianming Yu, Mitch Tuinstra, and Geoffrey P. Morris
In crop species, adaptation to different agroclimatic regions creates useful variation but also leads to unwanted genetic correlations. Bouchet et al. addressed this challenge in the cereal crop sorghum by developing a Nested Association Mapping (NAM) population, which reshuffles global genetic diversity for trait mapping. The NAM population consists of 2214 recombinant inbred lines genotyped at 90,000 markers, and was validated by map- ping flowering time and plant height. Simulated traits demonstrated the NAM is a powerful tool for dissecting traits under strong selection.
Genotypic complexity of Fisher’s geometric model, pp. 1049-1079
Sungmin Hwang, Su-Chan Park, and Joachim Krug
In his celebrated model of adaptation, Fisher assumed a smooth phenotype- fitness map with one optimum. This assumption is at odds with the rugged genotypic fitness landscapes with multiple peaks revealed by empirical studies. Hwang et al. performed a systematic analysis of the genotype-fitness map produced by Fisher’s model and show that these fitness landscapes actually can be remarkably complex. They provide a precise quantitative characterization of ruggedness as a function of phenotypic dimensionality and distance from the optimal phenotype.
The hippo pathway maintains the equatorial division plane in the ciliate Tetrahymena, pp. 873-888
Yu-Yang Jiang, Wolfgang Maier, Ralf Baumeister, Gregory Minevich, Ewa Joachimiak, Zheng Ruan, Natarajan Kannan, Diamond Clarke, Joseph Frankel, and Jacek Gaertig
The mechanisms governing organelle pattern formation in ciliates are still poorly understood. Jiang et al. investigate how the cell duplicates its cortical pattern during cell division in the ciliate Tetrahymena thermophila. They used whole genome sequencing to identify a mutation that causes asymmetric cell division. The identified protein is a Hippo/Mst kinase that marks the cortex of the emerging anterior daughter cell, and is required to keep the division plane at the cell’s equator.
Adipocyte Metabolic Pathways Regulated by Diet Control the Female Germline Stem Cell Lineage in Drosophila melanogaster, pp. 953-971
Shinya Matsuoka, Alissa R. Armstrong, Leesa L. Sampson, Kaitlin M. Laws, and Daniela Drummond-Barbosa
Proteomics analysis identifies orthologs of human chitinase-like proteins as inducers of tube morphogenesis defects in Drosophila melanogaster, pp. 973-984
Sandra G. Zimmerman, Gennifer E. Merrihew, Michael J. MacCoss, and Celeste A. Berg
Two papers in this issue demonstrate novel proteomic approaches that enhance genetic analysis. Matsuoka et al. investigated how diet-regulated metabolic pathways influence Drosophila germline stem cells. They used proteomic analysis to find regulatory enzymes that respond rapidly to diet. Genetic manipulation of their expression uncovered new metabolic controls of germline stem cells. Zimmerman et al. investigated Chitinase-like proteins (CLPs), which contribute to antipathogenic responses and wound healing but are elevated in numerous diseases. Drosophila orthologs of human CLPs were identified by proteomics analysis as regulators of tube morphogenesis; genetic alteration of their expression disrupted epithelial tube formation.
Structural variation shapes the landscape of recombination in mouse, pp. 603-619
Andrew P. Morgan, Daniel M. Gatti, Maya L. Najarian, Thomas M. Keane, Raymond J. Galante, Allan I. Pack, Richard Mott, Gary A. Churchill, and Fernando Pardo-Manuel de Villena
Meiotic recombination ensures the faithful segregation of chromosomes and influences patterns of genetic diversity. Morgan et al. used genotype data from 6,886 Diversity Outbred mice to study local variation in recombination rates and the impact of genetic diversity on crossover distribution. They found almost one-fourth of crossovers occur outside of putative recombination hot- spots identified by previous CHIP-seq experiments. Crossovers were also suppressed in genomic regions with copy number variation (CNV), perhaps because CNVs alter chromatin structure, preventing chromosomes carrying different structural alleles from pairing normally.
Genetic dissection of nutrition-induced plasticity in insulin/insulin-like growth factor signaling and median lifespan in a Drosophila multiparent population, pp. 587-602
Patrick D. Stanley, Enoch Ng’oma, Siri O’Day and Elizabeth G. King
The insulin/insulin-like growth factor signaling (IIS) and target of rapamycin (TOR) pathways have long been thought to be involved in how organ- isms respond to their nutritional environment. However, little is known about the genetic basis of naturally occurring variation in these pathways. In this study, Stanley et al. used a multiparent population to genetically dissect diet-dependent IIS/TOR expression and connect it to diet-dependent changes in lifespan.
Epistatic networks jointly influence phenotypes related to metabolic disease and gene expression in Diversity Outbred mice, pp. 621-639
Anna L. Tyler, Bo Ji, Daniel M. Gatti, Steven C. Munger, Gary A. Churchill, Karen L. Svenson, and Gregory W. Carter
In this study, Tyler et al. analyzed the complex genetic architecture of metabolic disease-related traits using the Diversity Outbred mouse population. By jointly analyzing epistasis across multiple phenotypes, they inferred a multi-scale network of quantitative trait loci (QTL) involving QTL-QTL, QTL-sex, and QTL-diet interactions that jointly influence body composition, serum markers, and transcriptome expression. They found that genetic contributions from different founder ancestries often combine to drive more extreme phenotypes, leading to the broad phenotypic diversity observed in this population.